Characterization of brain atrophy in Huntington's disease mouse model Abstract The proposed study is aimed at developing new image analysis techniques to characterize brain atrophy in the R6/2 mouse line, a mouse model of Huntington's disease (HD). Atrophy of specific brain structures is known to be an important marker of HD and other neurodegenerative diseases. The R6/2 line has progressive HD-like phenotypes, e.g. atrophy and motor deficits, and has been widely used in preclinical therapeutic trials. Although there exist histo-pathological and behavioral data of the R6/2 line, key aspects of atrophy in the brain, such as its spatial and temporal profiles, have not been full investigated. The information is important to understand the mechanism of disease progression and to develop new treatment. The technique proposed in this study is based on three major technical innovations: (i) in vivo MR "micro-imaging" for data acquisition, (ii) a detailed neuro-anatomical atlas of developing mouse brains for consistent parcellation of brain structures, and (iii) state-of-the-art computational neuroanatomy for quantification of atrophy and structural deformation. In this application, we will first validate the techniques and then apply the techniques to characterize atrophy in R6/2 mice and the effect of creatine treatment on atrophy, through in vivo longitudinal studies. PUBLIC HEALTH RELEVANCE: In this project, novel magnetic resonance imaging based analysis techniques will be developed to characterize the spatial and temporal profiles of atrophy in R6/2 mouse brain, a widely used model of Huntington's disease. Association between atrophy and neurodegeneration and the effect of creatine treatment will also be investigated.